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Pharmacology MBBS > Rheumatoid arthritis and gout > Flashcards

Rheumatoid arthritis and gout Flashcards

1
Q

Drugs used in rheumatoid arthritis

A 
For acute flair of RA:
1. NSAIDS 
2. Steroids (and bridging effect)
For treating the condition:
3. DMARDs: 
 •conventional
 •biological
 •small molecule kinase inhibitors
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2
Q

Examples of conventional DMARD

A
  1. Methotrexate
  2. Hydroxychloroquine
  3. Sulfasalazine
  4. Immunomodulators:
    •Cyclosporine
    •Azathioprine
    •Omecamtivmecarbil
  5. Leflunomide
  6. Cyclophosphamide
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3
Q

Biological DMARDs

A
  1. TNF-α inhibitors
  2. Abatacept
  3. IL-1 inhibitors: Anakinra
  4. IL-6 inhibitors:
    Tocilizumab, Sarilumab
  5. CD-20 inhibitors: Lituximab
    They downregulate immune system ➡️ opportunistic infections and are contraindicated with JAK inhibitors and each other
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4
Q

Examples of TNF-α inhibitors used as biological DMARDs

A
  1. Adalimumab
  2. Centolizumab
  3. Etanercept
  4. Golimumab
  5. Infliximumab
    All are given subcutaneous route
    Adalimumab and Infliximab can be given IV also
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5
Q

Examples of JAK inhibitors or small molecule kinase inhibitors used as DMARD

A
  1. Baricitinib
  2. Tofacitinib
  3. Upadacitinib

They downregulate immune system ➡️ opportunistic infections and are contraindicated with biological DMARDs and each other

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6
Q

Drugs used to treat acute flair of rheumatoid arthritis

A 
1. NSAIDS:
 Aspirin: 3-4g/day
2. Steroids:
 Oral: Prednisolone 
 Intra articular: Triamcinolone

Steroids are used for bridging effect since Methotrexate is effective after 2-4 weeks

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7
Q

Treatment of rheumatoid arthritis

A

Of naive:
DoC: methotrexate and steroids
If no response to maximum dose of methotrexate add:
1. Sulfasalazine and Hydroxychloroquine (or)
2. Leflunomide (or)
3. Biological drug (of no response change to another biological drug) (or)
4. JAK inhibitors

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8
Q

Methotrexate in rheumatoid arthritis

A

Conventional DMARD
Mechanism:
1. Inhibit purine synthesis ➡️ toxic to lymphocytes
2. Increased adenosine ➡️ anti inflammatory but causes hepatic fibrosis
DoC in rheumatoid arthritis (Anchor drug)
Side effects:
Hepatotoxicity ➡️ liver cirrhosis
Monitor ALT/AST every 3 months

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9
Q

Hydroxychloroquine in rheumatoid arthritis

A 
Conventional DMARD
•Mechanism:
1. Inhibits lymphocytes
2. Stabilises lysosomes
•Uses:
1. In mild cases, monotherapy 
2. In moderate/severe cases, as an add on drug
•Side effects- Bull’s eye retinopathy
 Dose <5 mg/kg/day
 Ophthalmological exam once a year
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10
Q

Sulfasalazine in rheumatoid arthritis

A 
Hybrid drug
Conventional DMARD
Metabolises into:
1. Sulfapyridine (absorbed)
2. 5-Amino salicylic acid:
 Not absorbed
 Used in ulcerated colitis
Mechanism: inhibits T and B lymphocytes
Uses: 
1. Mild cases - monotherapy 
2. Severe cases - add on drug
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11
Q

Uses of TNF-α inhibitors

A
  1. Rheumatoid arthritis
  2. Ankylosing spondylitis
  3. Psoriasis: plaque and arthritis
  4. Inflammatory bowel disease:
    ulcerative colitis and Crohn’s disease
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12
Q

Side effects of TNF-α inhibitors

A

G. GIT ulcer, perforation
O. Opportunistic infections ➡️ activation of TB
L. Lymphoma/ melanoma (2° cancer)
SLE (rare)

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13
Q

Absolute contraindications of TNF-α inhibitors

A
  1. CHF (severe): class III, IV

2. Hepatitis B

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14
Q

Anakinra

A

IL-1 inhibitor
Least effective biological drug in rheumatoid arthritis
Not preferred

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15
Q

IL-6 inhibitors used in rheumatoid arthritis

A

Both are used against rheumatoid arthritis- resistant cases
1. Tocilizumab:
Juvenile idiopathic arthritis (Still’s disease)
2. Sarilumab

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16
Q

Abatacept

A 
Biological DMARD  
Mechanism:
1. Inhibit CD 80/86 
2. Downregulate lymphocyte activation
Used in rheumatoid arthritis
Can cause infections

Belatacept is used in GVHD

17
Q

Uses of Tofacitinib

A 
JAK inhibitor
Oral drug
Uses:
1. Rheumatoid arthritis
2. Psoriatic arthritis
3. Ulcerative colitis 
(not effective in Crohn’s disease)
The 2 more recent drugs are approved only for rheumatoid arthritis
18
Q

JAK inhibitors used in rheumatoid arthritis

A

Tofacitinib, Baricitinib, Upadacitinib
Mechanism:
JAK inhibitor
Decreased proliferation of lymphocytes and erythrocytes

19
Q

Side effects of JAK inhibitors

A 
Tofacitinib, Baricitinib, Upadacitinib
Side effects: infections
1. GIT ulcer and proliferation
2. 2° cancer: non melanoma skin cancer
3. Hyperlipidemia
20
Q

Treatment of acute gout

A
  1. NSAIDS
    DoC- indomethacin
    If not responding to NSAIDs then steroids
  2. Colchicine
    Also used as a prophylactic in familial Mediterranean fever and amyloidosis
21
Q

Mechanism of action of colchicine against acute gout

A
  1. Inhibits microtubules
    ➡️ inhibits chemotaxis
    ➡️ inhibits migration of leukocytes into joints
  2. Inhibits phagocytosis
  3. Inhibits release of chemotactic factors by neutrophils like interleukin-1, leukotrine B4
22
Q

Side effects of colchicine

A
  1. GIT: most common
    Nausea, vomiting and diarrhoea
  2. Bone marrow suppression
  3. Alopecia
23
Q

Treatment of chronic gout

A 
1. Xanthine oxidase inhibitors:
 Inhibits RDS of uric acid synthesis
2. Uricosuric drugs
 Increases uric acid excretion
3. Enzymes:
 Metabolises uric acid
24
Q

Allopurinol

A

Xanthine oxidase inhibitor
Hypoxanthine analogue
Mechanism:
Competitive inhibitor of xanthine oxidase

25
Q

Uses of allopurinol

A 
Xanthine oxidase inhibitor
DoC to treat hyperuricemia in:
1. Chronic gout
2. Tumour lysis syndrome
3. Lesch Neyhan syndrome
4. Organ transplant patient
26
Q

Adverse effects of allopurinol

A
  1. Hypersensitivity (most common)
  2. Acute gout (compensatory):
    To prevent allopurinol induced acute gout, NSAID/colchicine for first 2 weeks.
  3. Inhibits orotidylate decarboxylase causing orotic aciduria.
  4. Xanthine stones
27
Q

Oxypurinol

A

Xanthine oxidase inhibitor
An orphan drug used to treat chronic gout in allopurinol hypersensitivity patients
Side effect: xanthine stones

28
Q

Febuxostat

A

Xanthine oxidase inhibitor like allopurinol and oxypurinol
Used in chronic gout
Side effect:
Xanthine stones

29
Q

Mechanism of action and uses of uricosuric agents

A 
Increases uric acid excretion
Used in chronic gout when:
1.  Xanthine oxidase ineffectiveness/ tolerance
2. Underexcretion of uric acid
3. Tophi are present
30
Q

Orphan receptor

A

Receptor without a known ligand

31
Q

Examples of uricosuric agents

A

Those which are not effective in renal failure:
1. Sulfinpyrazone
2. Probenecid
3. Losartan
4. Lesinurad
The most potent, hence effective in renal failure- benzbromarone

32
Q

Side effects of uricosuric agents

And contraindications

A
  1. Renal stones (adequate hydration required)
  2. Sulfapyrazone, probenecid cause GIT upset, aplastic anaemia
  3. Benzbromarone is hepatotoxic

CI: conditions with increased uric acid production

33
Q

Uricase analogues

A 
In birds:
Uric acid is converted into allantoin by uricase which is excreted into urine 
Examples (given IV):
1. Rasburicase: against tumour lysis syndrome
2. Pegloticase: resistant chronic gout
Side effects are:
1. Hypersensitivity
2. Haemolysis in G6PD deficiency
3. Methemoglobinemia

Pharmacology MBBS (19 decks)

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